TDP-43 M337V Mutation in Familial Amyotrophic Lateral Sclerosis in Japan

被引：39

作者：

Tamaoka, Akira ^{[1
]}

Arai, Makoto ^{[2
]}

Itokawa, Masanari ^{[2
]}

Arai, Tetsuaki ^{[2
]}

Hasegawa, Masato ^{[2
]}

Tsuchiya, Kuniaki ^{[3
]}

Takuma, Hiroshi ^{[1
]}

Tsuji, Hiroshi ^{[1
]}

Ishii, Akiko ^{[1
]}

Watanabe, Masahiko ^{[1
]}

Takahashi, Yuji ^{[4
]}

Goto, Jun ^{[4
]}

Tsuji, Shoji ^{[4
]}

Akiyama, Haruhiko ^{[2
]}

机构：

[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Doctoral Program Med Sci Control Pathol Proc, Dept Neurol, Tsukuba, Ibaraki, Japan

[2] Tokyo Inst Psychiat, Tokyo, Japan

[3] Tokyo Metropolitan Matsuzawa Hosp, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo, Japan

来源：

INTERNAL MEDICINE | 2010年 / 49卷 / 04期

关键词：

Amyotrophic lateral sclerosis (ALS); TAR-DNA-binding protein 43 (TDP-43); TARDBP MUTATIONS;

D O I：

10.2169/internalmedicine.49.2915

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The clinical features of a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (ALS) are reported. Weakness initially affected the bulbar musculature, with later involvement of the extremities. Genetic studies failed to detect any mutations of the Cu/Zn superoxide dismutase-1 (SOD1) and Dynactin1 (DCTN1) genes, but revealed a single base pair change from wild-type adenine to guanine at position 1009 in TAR-DNA-binding protein (TDP-43), resulting in a methionine-to-valine substitution at position 337. The immunohistochemical study on autopsied brain of the proband's aunt showed TDP-43-positive cytoplasmic inclusions in the anterior horn cells of the spinal cord and in the hypoglossal nucleus, as well as glial cytoplasmic inclusions in the precentral gyrus, suggesting that a neuroglial proteinopathy was related to TDP-43. In conclusion, a characteristic clinical phenotype of familial ALS with initial bulbar symptoms occurred in this family with TDP-43 M337V substitution, the pathomechanism of which should be elucidated.

引用

页码：331 / 334

页数：4

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